Chutani A, Norouzi S, Lerma EV. C3 glomerulopathy in transplant “like yet unlike native”: Pathophysiology, recent advances in therapeutics and evolving paradigms. World J Transplant 2026; 16(2): 117138 [DOI: 10.5500/wjt.v16.i2.117138]
Corresponding Author of This Article
Arun Chutani, MD, Assistant Professor, FACP, FASN, Renal Medicine, UMass Chan Medical School, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01655, United States. docarun26@gmail.com
Research Domain of This Article
Transplantation
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Transplant. Jun 18, 2026; 16(2): 117138 Published online Jun 18, 2026. doi: 10.5500/wjt.v16.i2.117138
C3 glomerulopathy in transplant “like yet unlike native”: Pathophysiology, recent advances in therapeutics and evolving paradigms
Arun Chutani, Sayna Norouzi, Edgar V Lerma
Arun Chutani, Renal Medicine, UMass Chan Medical School, UMass Memorial Medical Center, Worcester, MA 01655, United States
Sayna Norouzi, Department of Internal Medicine, Loma Linda University, Loma Linda, CA 92350, United States
Edgar V Lerma, University of Illinois at Chicago College of Medicine, Advocate Christ Medical Center, University of Illnois, Chicago, IL 60612, United States
Author contributions: Chutani A remains the main author regarding conceptualization and construct of the manuscript; Norouzi S and Lerma EV provided constructive feedback in organizing the manuscript in its present form.
AI contribution statement: Co-Pilot was used for grammar correction and sentence structure modification. The manuscript is not AI generated; it is self-written, but Co-pilot helped with grammar correction and sentence structure modification for improving coherence.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Arun Chutani, MD, Assistant Professor, FACP, FASN, Renal Medicine, UMass Chan Medical School, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01655, United States. docarun26@gmail.com
Received: December 2, 2025 Revised: February 10, 2026 Accepted: April 7, 2026 Published online: June 18, 2026 Processing time: 180 Days and 7.2 Hours
Core Tip
Core Tip: C3 glomerulopathy is the most frequent recurrent glomerular disease after kidney transplantation, with recurrence rates up to 90%. Its pathogenesis is driven by alternative complement pathway dysregulation, influenced by genetic mutations, autoantibodies, monoclonal gammopathy, and transplant-specific triggers such as ischemia-reperfusion injury and viral infections. Histopathology in the allograft often shows subtler C3 deposition compared with native disease, underscoring the need for protocol biopsies. Traditional immunosuppression offers limited benefit, while novel complement-targeted therapies - including factor B inhibitors (iptacopan), C3 inhibitors (pegcetacoplan), and factor D inhibitors - represent a paradigm shift. Early case reports in transplant recipients demonstrate promising outcomes, highlighting the importance of personalized medicine and early intervention to preserve graft survival.
